The effects of the GABA agonist, baclofen, on sleep and breathing

Abstract

The gamma aminobutyric acid (GABA)-B agonist, baclofen, is a centrally-acting, anti-spasmodic agent and muscle relaxant used in spinal cord lesions, multiple sclerosis and other neurological disorders. In a previous pilot study of quadriplegic patients, 75% of whom were treated with baclofen, we found a high prevalence of sleep-disordered breathing. Because of the depressant effects of GABA on the central nervous system, we hypothesized that baclofen might aggravate sleep-disordered breathing in susceptible individuals by depressing central ventilatory drive, increasing upper airway obstruction and/or increasing the arousal threshold to apnoea. We therefore conducted a double-blind, placebo-controlled, cross-over study of baclofen 25 mg, administered before sleep in 10 snorers with mild sleep-disordered breathing (respiratory disturbance index <30 events per sleep hour). Each subject underwent two standard polysomnographic assessments, one week apart. Total sleep time was significantly prolonged by baclofen (placebo 356 ± 9.9 SEM min; baclofen 386 ± 9.9 min). Both nonrapid eye movement(REM) and IBM sleep duration were increased (nonREM: placebo 295 ± 6.8 min; baclofen 311 ± 8.9 min; REM: placebo 61 ± 7.5 min; baclofen 76 ± 9.0 min). Time spent awake after sleep onset was reduced after baclofen (placebo 71 ± 10.3 min; baclofen 51 ± 9.7 min). There was a slight reduction in mean overnight Oxygen saturation (placebo 95.2 ± 0.5%; baclofen 94.4 ± 0.7%). The frequency of apnoeas plus hypopnoeas (respiratory disturbance index (RDI)) did not change significantly (placebo 9 ± 1.8 events · h-1; baclofen 13 ± 3.4 events · h-1. We conclude that a single, therapeutic dose of baclofen alters sleep architecture and produces a small reduction in mean sleep oxygen saturation, but does not significantly increase sleep-disordered breathing.